Department of Clinical and Molecular Medicine, Sapienza University of Rome, Rome, Italy.
AOU Policlinico Umberto I, Rome, Italy.
J Transl Med. 2020 Feb 3;18(1):49. doi: 10.1186/s12967-020-02231-0.
Despite the efficacy of immune checkpoint inhibitors (ICIs) only the 20-30% of treated patients present long term benefits. The metabolic changes occurring in the gut microbiota metabolome are herein proposed as a factor potentially influencing the response to immunotherapy.
The metabolomic profiling of gut microbiota was characterized in 11 patients affected by non-small cell lung cancer (NSCLC) treated with nivolumab in second-line treatment with anti-PD-1 nivolumab. The metabolomics analyses were performed by GC-MS/SPME and H-NMR in order to detect volatile and non-volatile metabolites. Metabolomic data were processed by statistical profiling and chemometric analyses.
Four out of 11 patients (36%) presented early progression, while the remaining 7 out of 11 (64%) presented disease progression after 12 months. 2-Pentanone (ketone) and tridecane (alkane) were significantly associated with early progression, and on the contrary short chain fatty acids (SCFAs) (i.e., propionate, butyrate), lysine and nicotinic acid were significantly associated with long-term beneficial effects.
Our preliminary data suggest a significant role of gut microbiota metabolic pathways in affecting response to immunotherapy. The metabolic approach could be a promising strategy to contribute to the personalized management of cancer patients by the identification of microbiota-linked "indicators" of early progressor and long responder patients.
尽管免疫检查点抑制剂（ICIs）有效，但只有 20-30%的治疗患者有长期获益。肠道微生物组代谢物的代谢变化被提出是可能影响免疫治疗反应的因素之一。
11 名患有非小细胞肺癌（NSCLC）的患者接受纳武单抗二线治疗（抗 PD-1 纳武单抗），对其肠道微生物组的代谢组学特征进行了描述。通过 GC-MS/SPME 和 H-NMR 进行代谢组学分析，以检测挥发性和非挥发性代谢物。代谢组学数据通过统计分析和化学计量学分析进行处理。
11 名患者中有 4 名（36%）出现早期进展，而其余 7 名（64%）在 12 个月后出现疾病进展。2-戊酮（酮）和十三烷（烷烃）与早期进展显著相关，而短链脂肪酸（SCFAs）（即丙酸、丁酸）、赖氨酸和烟酰胺则与长期有益反应显著相关。
我们的初步数据表明，肠道微生物组代谢途径在影响免疫治疗反应方面具有重要作用。代谢方法可能是通过识别与早期进展者和长期应答者相关的“指标”，为癌症患者的个性化管理做出贡献的有前途的策略。
